Association of intestinal bacteria with immune activation in a cohort of healthy adults

Authors: RIAZATI, NIKNAZ - University Of California, Davis; Kable, Mary; Stephensen, Charles

Submitted to: Microbiology Spectrum
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/11/2023
Publication Date: 10/11/2023
Citation: Riazati, N., Kable, M.E., Stephensen, C.B. 2023. Association of intestinal bacteria with immune activation in a cohort of healthy adults. Microbiology Spectrum. 11(6). Article e0102723. https://doi.org/10.1128/spectrum.01027-23.
DOI: https://doi.org/10.1128/spectrum.01027-23

Interpretive Summary: Bacteria living in the intestine interact with the intestinal immune system, contributing to the maintenance of intestinal barrier integrity in healthy individuals. The goal of our study was to identify bacteria that are associated with markers of systemic inflammation and immune activation in healthy adults. To test this hypothesis, we examined association between intestinal bacteria and immune variables in 355 healthy men and women 18-65 years old who had normal body weight or were overweight, or obese. 79 immune variables were measured from the study participant’s blood samples and bacterial abundances were measured from their stool samples. We used a statistical model called generalized linear regression model to identify bacteria that were associated with the immune markers. We found 10 statistically significant associations between intestinal bacteria and immune markers. Among them, Rikenellaceae, Pseudomonadaceae and Pseudomonas were associated with markers of innate immune response and Rikenellaceae, Slackia and Butyrivibrio were associated with markers of adaptive immune response. Our results indicate that there might be an ongoing effect of these intestinal bacteria on specific aspects of innate and adaptive immunity in healthy adults. These results further suggest that some of these associations represent a contribution to a healthy intestinal barrier.

Technical Abstract: Background Interactions among intestinal bacteria and the immune system through the intestinal mucosa and epithelium contribute to the maintenance of a functional intestinal barrier in healthy individuals, and possibly to systemic immune activity. In this study, we hypothesized that intestinal bacteria would be associated with systemic biomarkers of innate and adaptive immune responses in healthy adults. Methods 79 immune function markers were subjected to factor analysis in SAS, resulting in 17 Immune Factors (IFs), each comprised of 2 to 10 highly correlated immune variables. Bacterial taxa from stool samples were identified at the family and genus levels by 16S rRNA amplicon sequence analysis and their read counts and relative abundances were utilized in a multiple linear regression model to identify microbial taxa associated with the IFs. Result A total of 10 significant associations were identified between gut microbial taxa and IFs. Among these, family Rikenellaceae showed a positive association with innate IF5 (innate variables including 5 chemokines, 2 cytokines, 2 adhesion molecules and the macrophage metabolite neopterin) and a negative association with adaptive IF4 (adaptive variables including T-cells with activation marker HLA-DR). Additionally, Pseudomonadaceae and its genus Pseudomonas showed a positive relationship with innate IF5, while adaptive IF13 (adaptive variables including T-cell cytokines IL-10, IL-17 and IFN-') was negatively associated with Butyrivibrio and positively associated with Slackia. Conclusion The identified significant associations suggest ongoing interactions between gut bacteria and the innate and adaptive components of the systemic immune function in heathy individuals. Also, the associations of the identified microbial taxa with the IFs may be indicative of the specific microbial-immune system interactions that play a role in maintenance of a healthy barrier integrity in our cohort of healthy adults.